EP1671638A1 - Solutions de diphosphonates - Google Patents
Solutions de diphosphonates Download PDFInfo
- Publication number
- EP1671638A1 EP1671638A1 EP06007027A EP06007027A EP1671638A1 EP 1671638 A1 EP1671638 A1 EP 1671638A1 EP 06007027 A EP06007027 A EP 06007027A EP 06007027 A EP06007027 A EP 06007027A EP 1671638 A1 EP1671638 A1 EP 1671638A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- solution
- pharmaceutical product
- product according
- glass
- polymer
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/66—Phosphorus compounds
- A61K31/662—Phosphorus acids or esters thereof having P—C bonds, e.g. foscarnet, trichlorfon
- A61K31/663—Compounds having two or more phosphorus acid groups or esters thereof, e.g. clodronic acid, pamidronic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/02—Inorganic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
Definitions
- This invention relates to stable injectable solutions containing diphosphonates.
- diphosphonic acids can be used as therapeutic active agents for the treatment of hypercalcaemia and in medication for the treatment of diseases such as osteoporosis and tumor osteolysis.
- the active agent will be present as anions and is generally called diphosphonate, bisphosphonate or biphosphonate.
- An injection solution of diphosphonate can be prepared from the diphosphonic acid or one of its salts.
- a convenient method for administering these active agents is by intravenous infusion of prepared solutions into the bloodstream of a patient to be treated.
- excipients such as polyethylene glycols or acid buffers such as organic acids. Whilst the use of such excipients may assist, it is generally preferable to minimise the number of additional constituents of any injectable product solution.
- This invention provides a stable and preprepared injectable solution of diphosphonate ready to be diluted by a practitioner administering the product to the patient. This enables the product to be provided in a consistent quality and avoids the need for the practitioner to reconstitute the active agent at the time of administration.
- the present invention provides a pharmaceutical product comprising a container containing a diphosphonate in solution, wherein the solution:
- the present invention provides a pharmaceutical product comprising a container containing a diphosphonate in solution, wherein the solution:
- the present invention provides a pharmaceutical product comprising a container containing a diphosphonate in solution, wherein the solution:
- the present invention provides a method of preparing a pharmaceutical product, said method comprising the steps of:
- Appropriate containers for this product include ampoules, vials, bottles, ready to use syringes and Shell Glass Vials.
- a preferred method of pre-treatment is a siliconization process using a one percent silicone solution to wash the vials, followed by double draining and heating at 310°C for thirty minutes. Vials pretreated in this manner are available from the French vial manufacturer Saint-Gobain Desjonqueres (SGD).
- vial pretreatment techniques include the use of a high purity SiO 2 barrier formed on the inside vial surface by a plasma-deposition process.
- the process involves microwave energy being applied to a silicon containing precursor in the presence of oxygen.
- a plasma forms and a SiO 2 layer is formed on the glass surface from the gas phase.
- Vials pretreated in this manner are available from Schott.
- containers which are made from glass having a low aluminium content.
- Glass typically used for pharmaceutical vials has in the order of 5 percent aluminium oxide.
- glass with lower aluminium content is recommended.
- the stopper provides a potential source of contamination.
- Typical elastomeric stoppers are potentially a source of metal ions eg calcium, zinc and magnesium ions which can react with the diphosphonate to form insoluble matter.
- stoppers with low levels of these ions and other potential contaminants are to be used, preferably coated to form an inert barrier.
- An example of an appropriate stopper is the Daikyo D777-1 stopper. Daikyo D777-3 stoppers may also be used.
- the stopper has a low calcium, magnesium and ash content and is at least coated on the contact surface (being the surface of the stopper which when placed in a vial is exposed to the contents of the vial) with a fluorinated resin such as tetrafluoroethylene polymer, trifluorochloroethylene polymer, tetrafluoroethylene-hexafluoropropylene copolymer, fluorovinylidene polymer, vinylidene fluoride polymer, vinyl fluoride polymer, tetrafluoroethylene-ethylene copolymer, ethylene-tetrafluoroethylene copolymer, or perfluoroalkoxy polymer.
- a fluorinated resin such as tetrafluoroethylene polymer, trifluorochloroethylene polymer, tetrafluoroethylene-hexafluoropropylene copolymer, fluorovinylidene polymer, vinylidene fluoride polymer, vinyl fluoride polymer
- the stopper is coated with a fluorinated resin selected from a group consisting of tetrafluoroethylene polymer, trifluorochloroethylene polymer, tetrafluoroethylene-hexafluoropropylene copolymer, vinylidene fluoride polymer, vinyl fluoride polymer, and tetrafluoroethylene-ethylene copolymer.
- a fluorinated resin selected from a group consisting of tetrafluoroethylene polymer, trifluorochloroethylene polymer, tetrafluoroethylene-hexafluoropropylene copolymer, vinylidene fluoride polymer, vinyl fluoride polymer, and tetrafluoroethylene-ethylene copolymer.
- the stopper can be a FluroTec® stopper manufactured by Daikyo and distributed by West Pharmaceuticals Services.
- Containers such as vials, may be constructed from any suitable other materials in addition to glass, such as polyethylene, polypropylene and polymethylpentene.
- the vial could be constructed from Crystal Zenith® resin as manufactured by West Pharmaceuticals Services.
- This invention is generally applicable to all diphosphonates. Specifically, this includes solutions of pamidronate, zolindronate, chlodronate, etidronate, alendronate and tiludronate. These can be prepared from their respective diphosphonic acid form or from a therapeutically acceptable salt form.
- the acids of the above diphosphonates are:- pamidronic acid [(3-amino-1-hydroxypropylidene) diphosphonic acid], zoledronic acid [(1)-hydroxy-2-(1H-imidazol-1-yl)ethylidene) diphosphonic acid]; chlodronic acid [dichloromethylene disphosphonic acid]; etidronic acid [(1-hydroxyethylidene) diphosphonic acid]; alendronic acid [(4-amino-1-hydroxy-butylidene diphosphonic acid]; and tiludronic acid [[((p-chloro-phenyl)thio)methylene] diphosphonic acid] respectively.
- This invention is particularly applicable to pamidronate and zolendronate.
- a product within the biological pH range i.e. of between about 5 and 8, to reduce the incidence of potential adverse reactions relating to acidic or alkaline solutions. Surprisingly it has been found that a stable solution can be produced having a pH of 5 - 8. A pH level of approximately 6.5 is preferred. At pH levels below about 5 there is a risk of producing venous type irritations and other unwanted side effects. pH levels above about 8 give rise to generally unacceptable levels of turbidity.
- Solutions of diphosphonates will generally have a pH above that desired.
- a solution of one percent pamidronate disodium salt in distilled water has a pH of approximately 8.3.
- the pH is adjusted with a suitable acid or alkali.
- Suitable acids include any acid such as hydrochloric or phosphoric acid. Phosphoric acid is preferred.
- Suitable alkalis include sodium hydroxide.
- sugar alcohols and sodium chloride and water may be included in the solution, as required.
- Mannitol is the preferred sugar alcohol.
- Pamidronate solutions are preferably prepared by slowly adding sodium hydroxide solution to a suspension of pamidronic acid in water in a 2:1 molar ratio of sodium hydroxide to pamidronic acid, adding mannitol if desired, mixing by stirring until both pamidronic acid and mannitol (if appropriate) are completely dissolved and adjusting the pH with phosphoric acid and if necessary sodium hydroxide solution.
- Preferably the preparation of the solutions is carried out under nitrogen.
- Other diphosphonate solutions can be prepared in analogous fashion.
- a different closed mixing vessel is flushed with nitrogen gas for at least 15 minutes. Approximately 70% of the Water for Injection is added to the closed mixing vessel through a port and the mixing bubbled with nitrogen gas for at least 15 minutes. Pamidronic acid is then added to the mixing vessel with stirring and mixed for 5 minutes giving a suspension. The sodium hydroxide solution is then added over a 5 minute period with stirring to give a clear solution. Mannitol is then added to the solution with stirring for at least 5 minutes until dissolved.
- the pH is then checked and adjusted to a range of between 5 and 8 preferably, between 6.3 and 6.7 by addition of 1.0N phosphoric acid at the rate of approximately 12.1 g/L (calculated on total batch size) and if necessary 1.0N sodium hydroxide, whilst keeping the temperature between 35°C and 45°C.
- the volume is adjusted to the required level with Water for Injection and the solution cooled to below 30°C.
- the pH is then rechecked and adjusted if necessary to between 6.3 and 6.7, with 1.0N phosphoric acid or 1.0N sodium hydroxide if and as necessary.
- the product solution was composed of the following: pamidronic acid 2.53 mg mannitol 47.0 mg sodium hydroxide 0.43 mg pH qs to 6.3-6.7 using 1.0N sodium hydroxide or 1.0N phosphoric acid Water for Injection qs to 1.0 mL
- the formulated solution was filled into 10 mL siliconised, low aluminium, Type I glass vials, supplied by SGD. Each vial was enclosed by a 20 mm, S10-F451, D777-1, B2-40, FluroTec® stopper supplied by West Pharmaceuticals Services.
- Table 1 shows the test results measured over a 24 month period while being stored inverted at 25°C, relative humidity (RH) 60%.
- Table 1 Initial (0 months) 6 months 12 months 18 months 24months Appearance N N N N N N Potency 98.7% 99.9% 99.8% 100.1% 99.1 pH 6.4 6.2 6.3 6.4 6.5
- the product solution was composed of the following: pamidronic acid 7.58 mg mannitol 37.5 mg sodium hydroxide 1.29 mg pH qs to 6.3-6.7 using 1.0N sodium hydroxide or 1.0N phosphoric acid Water For Injection qs to 1.0 mL
- the formulated solution was filled into 10 mL siliconised, low aluminium, Type I glass vials, supplied by SGD. Each vial was enclosed by a 20 mm, S10-F451, D777-1, B2-40, Fluro Tec® stopper supplied by West Pharmaceuticals Services.
- Table 2 shows the test results measured over a 24 month period while being stored inverted at 25°C, relative humidity (RH) 60%.
- Table 2 Initial (0 months) 6 months 12 months 18 months 24 months Appearance N N N N N N Potency 100.2% 101.9% 100.4% 102.3% 101.1 pH 6.4 6.3 6.4 6.3 6.5
- the product solution was composed of the following: pamidronic acid 2.53 mg mannitol 47.0 mg sodium hydroxide 0.86 mg pH qs to 6.3-6.7 using 1.0N sodium hydroxide or 1.0N phosphoric acid. Water For Injection qs to 1.0 mL
- the formulated solution was filled into 10 mL siliconised, low aluminium, Type I glass vials, supplied by SGD. Each vial was enclosed by a 20 mm, S10-F451, D777-1, B2-40, Fluro Tec® stopper supplied by West Pharmaceuticals Services.
- Table 3 shows the test results measured over a 21 month period while being stored inverted at 25°C, relative humidity (RH) 60%.
- Table 3 Initial (0 months) 6 months 12 months 18 months 21 months Appearance N N N N N N Potency 103.6% 103.5% 104.0% 104.0 104.5 pH 6.5 6.4 6.5 6.6 6.5
- the product solution was composed of the following: pamidronic acid 7.58 mg mannitol 37.5 mg sodium hydroxide 2.58 mg pH qs to 6.3-6.7 using 1.0N sodium hydroxide or 1.0N phosphoric acid. Water For Injection qs to 1.0 mL
- the formulated solution was filled, into 10 mL siliconised, low aluminium, Type I glass-vials, supplied by SGD. Each vial was enclosed by a 20 mm, S10-F451, D777-1, B2-40, FluroTec® stopper supplied by West Pharmaceuticals Services.
- Table 4 shows the test results measured over a 21 month period while being stored inverted at 25°C, relative humidity (RH) 60%.
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Physical Education & Sports Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Rheumatology (AREA)
- Inorganic Chemistry (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Dermatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Detergent Compositions (AREA)
- Medicinal Preparation (AREA)
- Medical Preparation Storing Or Oral Administration Devices (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AUPR0189A AUPR018900A0 (en) | 2000-09-18 | 2000-09-18 | Pamidronate solution |
AUPR4855A AUPR485501A0 (en) | 2001-05-10 | 2001-05-10 | Stable injectable solutions |
EP01973807A EP1318818A4 (fr) | 2000-09-18 | 2001-09-18 | Solutions de diphosphonate |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP01973807A Division EP1318818A4 (fr) | 2000-09-18 | 2001-09-18 | Solutions de diphosphonate |
Publications (1)
Publication Number | Publication Date |
---|---|
EP1671638A1 true EP1671638A1 (fr) | 2006-06-21 |
Family
ID=25646444
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP01973807A Withdrawn EP1318818A4 (fr) | 2000-09-18 | 2001-09-18 | Solutions de diphosphonate |
EP06007027A Withdrawn EP1671638A1 (fr) | 2000-09-18 | 2001-09-18 | Solutions de diphosphonates |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP01973807A Withdrawn EP1318818A4 (fr) | 2000-09-18 | 2001-09-18 | Solutions de diphosphonate |
Country Status (10)
Country | Link |
---|---|
US (3) | US20040082545A1 (fr) |
EP (2) | EP1318818A4 (fr) |
KR (1) | KR20030043931A (fr) |
CN (1) | CN1441674A (fr) |
AU (1) | AU2001293473A1 (fr) |
CA (1) | CA2406446A1 (fr) |
NO (1) | NO20031215L (fr) |
PL (1) | PL360910A1 (fr) |
TW (1) | TW200418494A (fr) |
WO (1) | WO2002022136A1 (fr) |
Families Citing this family (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
MY141763A (en) * | 2003-09-18 | 2010-06-30 | Novartis Ag | Pharmaceutical products comprising bisphosphonates |
WO2006100687A1 (fr) * | 2005-03-24 | 2006-09-28 | Dabur Pharma Ltd. | Formulation aqueuse de pamidronate de disodium |
US7605148B2 (en) * | 2007-04-16 | 2009-10-20 | Aurobindo Pharma Ltd. | Aqueous oral solution of bisphosphonic acid |
EP2363111A1 (fr) * | 2010-03-01 | 2011-09-07 | Combino Pharm, S.L. | Composition pharmaceutique stable comprenant du bisphosphonate |
AR075721A1 (es) * | 2010-03-05 | 2011-04-20 | Eriochem Sa | Composicion farmaceutica que comprende una solucion de acido zoledronico. |
KR20120121403A (ko) * | 2010-04-16 | 2012-11-05 | 티티와이 바이오팜 캄파니 리미티드 | 디포스포네이트 주사액 의약품 및 그 제법 |
CN116077446A (zh) * | 2022-12-16 | 2023-05-09 | 上药东英(江苏)药业有限公司 | 一种雷贝拉唑钠冻干粉针剂及其制备方法 |
Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5219556A (en) * | 1990-07-09 | 1993-06-15 | Mallinckrodt Medical, Inc. | Stabilized therapeutic radiopharmaceutical complexes |
JPH0892102A (ja) * | 1994-09-26 | 1996-04-09 | Yamanouchi Pharmaceut Co Ltd | ビスホスホン酸又はその誘導体を含有する注射液とその安定化方法、及び注射液アンプル |
US5914323A (en) * | 1994-08-24 | 1999-06-22 | Merck & Co., Inc. | Intravenous alendronate formulations |
WO2000034293A1 (fr) * | 1998-12-10 | 2000-06-15 | Aesgen, Inc. | Methode de preparation du pamidronate |
WO2000035500A1 (fr) * | 1998-12-15 | 2000-06-22 | Bausch & Lomb Incorporated | Agent nettoyant pour lentilles de contact contenant du biguanide et une poloxamine |
EP1136069A1 (fr) * | 2000-03-21 | 2001-09-26 | SPA SOCIETA' PRODOTTI ANTIBIOTICI S.p.A. | Compositions pharmaceutiques comprenant des clodronates ayant une haute tolérance locale de l'administration intramusculaire |
Family Cites Families (15)
Publication number | Priority date | Publication date | Assignee | Title |
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SE7612534L (sv) * | 1975-12-01 | 1977-06-02 | Henkel & Cie Gmbh | Forfarande for framstellning av farmaceutiska preparat for behandling av storningar i kalciumemnesomsettning |
US4304734A (en) * | 1980-10-16 | 1981-12-08 | Vysoka Skola Chemicko-Technologicka | 6-Amino-1-hydroxyhexylidene diphosphonic acid, salts and a process for production thereof |
US4639338A (en) * | 1984-08-06 | 1987-01-27 | Ciba-Geigy Corporation | Preparation of crystalline disodium 3-amino-1-hydroxypropane-1,1-diphosphonate pentahydrate |
US5167816A (en) * | 1990-08-20 | 1992-12-01 | Abbott Laboratories | Sterile coupling device for drug container |
DE4228552A1 (de) * | 1992-08-27 | 1994-03-03 | Boehringer Mannheim Gmbh | Diphosphonsäuren und deren Salze enthaltende Arzneimittel |
US5853894A (en) * | 1997-02-03 | 1998-12-29 | Cytonix Corporation | Laboratory vessel having hydrophobic coating and process for manufacturing same |
US6087350A (en) * | 1997-08-29 | 2000-07-11 | University Of Pittsburgh Of The Commonwealth System Of Higher Education | Use of pretreatment chemicals to enhance efficacy of cytotoxic agents |
US6174873B1 (en) * | 1998-11-04 | 2001-01-16 | Supergen, Inc. | Oral administration of adenosine analogs |
US6160165A (en) * | 1998-12-10 | 2000-12-12 | Aesgen, Inc. | Method for preparation of disodium pamidronate |
US6794536B1 (en) * | 1998-12-10 | 2004-09-21 | Aesqen, Inc. | Method for preparation of disodium pamidronate |
US6167369A (en) * | 1998-12-23 | 2000-12-26 | Xerox Company | Automatic language identification using both N-gram and word information |
IL145470A0 (en) * | 1999-03-22 | 2002-06-30 | Immugen Pharmaceuticals Inc | Compositions for the treatment of immune diseases |
US6211169B1 (en) * | 1999-09-29 | 2001-04-03 | Aesgen, Inc. | Stable calcitriol solution for packaging into vials |
DE20106394U1 (de) * | 2001-04-11 | 2001-08-09 | Helm Pharmaceuticals Gmbh | Pharmazeutische Zubereitung |
MXPA03009890A (es) * | 2001-05-02 | 2004-02-17 | Sicor Inc | Pamidronato disodico inyectable. |
-
2001
- 2001-09-18 PL PL36091001A patent/PL360910A1/xx not_active Application Discontinuation
- 2001-09-18 CN CN01812743A patent/CN1441674A/zh active Pending
- 2001-09-18 EP EP01973807A patent/EP1318818A4/fr not_active Withdrawn
- 2001-09-18 KR KR10-2003-7002186A patent/KR20030043931A/ko not_active Application Discontinuation
- 2001-09-18 CA CA002406446A patent/CA2406446A1/fr not_active Abandoned
- 2001-09-18 US US10/380,645 patent/US20040082545A1/en not_active Abandoned
- 2001-09-18 WO PCT/AU2001/001171 patent/WO2002022136A1/fr not_active Application Discontinuation
- 2001-09-18 EP EP06007027A patent/EP1671638A1/fr not_active Withdrawn
- 2001-09-18 AU AU2001293473A patent/AU2001293473A1/en not_active Abandoned
- 2001-09-19 TW TW093111927A patent/TW200418494A/zh unknown
-
2003
- 2003-03-17 NO NO20031215A patent/NO20031215L/no not_active Application Discontinuation
-
2005
- 2005-07-26 US US11/190,493 patent/US20060154900A1/en not_active Abandoned
- 2005-07-28 US US11/194,106 patent/US20060154898A1/en not_active Abandoned
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5219556A (en) * | 1990-07-09 | 1993-06-15 | Mallinckrodt Medical, Inc. | Stabilized therapeutic radiopharmaceutical complexes |
US5914323A (en) * | 1994-08-24 | 1999-06-22 | Merck & Co., Inc. | Intravenous alendronate formulations |
JPH0892102A (ja) * | 1994-09-26 | 1996-04-09 | Yamanouchi Pharmaceut Co Ltd | ビスホスホン酸又はその誘導体を含有する注射液とその安定化方法、及び注射液アンプル |
WO2000034293A1 (fr) * | 1998-12-10 | 2000-06-15 | Aesgen, Inc. | Methode de preparation du pamidronate |
WO2000035500A1 (fr) * | 1998-12-15 | 2000-06-22 | Bausch & Lomb Incorporated | Agent nettoyant pour lentilles de contact contenant du biguanide et une poloxamine |
EP1136069A1 (fr) * | 2000-03-21 | 2001-09-26 | SPA SOCIETA' PRODOTTI ANTIBIOTICI S.p.A. | Compositions pharmaceutiques comprenant des clodronates ayant une haute tolérance locale de l'administration intramusculaire |
Non-Patent Citations (1)
Title |
---|
PATENT ABSTRACTS OF JAPAN vol. 1996, no. 08 30 August 1996 (1996-08-30) * |
Also Published As
Publication number | Publication date |
---|---|
AU2001293473A1 (en) | 2002-03-26 |
PL360910A1 (en) | 2004-09-20 |
CA2406446A1 (fr) | 2002-03-21 |
NO20031215L (no) | 2003-05-16 |
CN1441674A (zh) | 2003-09-10 |
US20040082545A1 (en) | 2004-04-29 |
WO2002022136A1 (fr) | 2002-03-21 |
EP1318818A4 (fr) | 2004-09-29 |
EP1318818A1 (fr) | 2003-06-18 |
US20060154900A1 (en) | 2006-07-13 |
NO20031215D0 (no) | 2003-03-17 |
KR20030043931A (ko) | 2003-06-02 |
US20060154898A1 (en) | 2006-07-13 |
TW200418494A (en) | 2004-10-01 |
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